A Toxin-Antitoxin Module of Salmonella Promotes Virulence in Mice

Abstract

Toxin-antitoxin (TA) modules are widely prevalent in both bacteria and archaea. Originally described as stabilizing elements of plasmids, TA modules are also widespread on bacterial chromosomes. These modules promote bacterial persistence in response to specific environmental stresses. So far, the possibility that TA modules could be involved in bacterial virulence has been largely neglected, but recent comparative genomic studies have shown that the presence of TA modules is significantly associated with the pathogenicity of bacteria. Using Salmonella as a model, we investigated whether TA modules help bacteria to overcome the stress conditions encountered during colonization, thereby supporting virulence in the host. By bioinformatics analyses, we found that the genome of the pathogenic bacterium Salmonella Typhimurium encodes at least 11 type II TA modules. Several of these are conserved in other pathogenic strains but absent from non-pathogenic species indicating that certain TA modules might play a role in Salmonella pathogenicity. We show that one TA module, hereafter referred to as sehAB, plays a transient role in virulence in perorally inoculated mice. The use of a transcriptional reporter demonstrated that bacteria in which sehAB is strongly activated are predominantly localized in the mesenteric lymph nodes. In addition, sehAB was shown to be important for the survival of Salmonella in these peripheral lymphoid organs. These data indicate that the transient activation of a type II TA module can bring a selective advantage favouring virulence and demonstrate that TA modules are engaged in Salmonella pathogenesis.

MazF ribonucleases promote Mycobacterium tuberculosis drug tolerance and virulence in guinea pigs

“…The growth defect was more prominent in the spleen and the liver than the lungs, indicating that MazF toxins may play a major role in the dissemination of the disease from the lungs to the spleen and liver. TA systems have also been reported to contribute to the virulence of other pathogens such as Haemophilus influenzae, Salmonella and enteropathogenic E. coli 53,66,67 . These results suggest that MazF ribonucleases enable Mtb to survive the environmental stresses (for example, oxidative and nutritional stresses) and/or immune responses encountered in the host.…”

Functional and Structural Analysis of HicA3-HicB3, a Novel Toxin-Antitoxin System of Yersinia pestis

“…A few TASs have been shown to be involved in virulence in Salmonella enterica (47), Haemophilus influenzae (48), and Mycobacterium tuberculosis (49). We suggested previously that hicB3 may be involved in plague pathogenesis (3).…”

Genomic and Phenotypic Analyses Reveal the Emergence of an Atypical Salmonella enterica Serovar Senftenberg Variant in China

“…For instance, the SC1 isolates (all except S09008) share the genes encoding the YeeV-YeeU toxin-antitoxin system that has been identified in many prokaryotic genomes and is associated with the enhanced persistence of bacteria in response to environmental stress (50,51). Recently, this toxin-antitoxin module has been shown to promote the colonization and survival of Salmonella in mouse mesenteric lymph nodes (52).…”